Prognostic Impact of Breast-Conserving Therapy Versus Mastectomy of BRCA1/2 Mutation Carriers Compared With Noncarriers in a Consecutive Series of Young Breast Cancer Patients

Abstract

Objective: To investigate the effects of different types of surgery on breast cancer prognosis in germline BRCA1/BRCA2 mutation carriers compared with noncarriers.

Summary of background data: Although breast-conserving therapy (breast-conserving surgery followed by radiotherapy) has been associated with more local recurrences than mastectomy, no differences in overall survival have been found in randomized trials performed in the general breast cancer population. Whether breast-conservation can be safely offered to BRCA1/2 mutation carriers is debatable.

Methods: The study comprised a cohort of women with invasive breast cancer diagnosed <50 years and treated between 1970 and 2003 in 10 Dutch centers. Germline DNA for BRCA1/2 testing of most-prevalent mutations (covering ∼61%) was mainly derived from paraffin-blocks. Survival analyses were performed taking into account competing risks.

Results: In noncarriers (N = 5820), as well as in BRCA1 (N = 191) and BRCA2 (N = 70) mutation carriers, approximately half of the patients received breast-conserving therapy. Patients receiving mastectomy followed by radiotherapy had prognostically worse tumor characteristics and more often received systemic therapy. After adjustment for these potential confounders, patients who received breast-conserving therapy had a similar overall survival compared with patients who received mastectomy, both in noncarriers (hazard ratio [HR] = 0.95, confidence interval [CI] = 0.85-1.07, P = 0.41) and BRCA1 mutation carriers (HR = 0.80, CI = 0.42-1.51, P = 0.50). Numbers for BRCA2 were insufficient to draw conclusions. The rate of local recurrences after breast-conserving therapy did not differ between BRCA1 carriers (10-year risk = 7.3%) and noncarriers (10-year risk = 7.9%).

Conclusion: Our results, together with the available literature, provide reassurance that breast-conserving therapy is a safe local treatment option to offer to BRCA1 mutation carriers with invasive breast cancer.